The goal of the proposed work is to evaluate mercaptoethylguanidine (MEG) as a drug to slow or reverse the immune system-derived damage in diabetes. Islet cell destruction in diabetes is caused by an autoimmune process. Key steps in the final islet cell destruction pathway are production of 1) the toxic oxidant peroxynitrite, 2) the free radical nitric oxide, and 3) thromboxane. MEG is a potent scavenger of peroxynitrite, a potent inhibitor of nitric oxides synthase (NOS), with specificity for the inducible form of NOS, and a moderately potent inhibitor of inducible cyclooxygenase. Inotek is a start-up company formed to explore uses of MEG (and other mercaptoalkylguanidines) in the treatment of inflammatory disorders. The purpose of this Phase I study is to synthesize large quantities of MEG and to test whether this drug can slow down or reverse the onset of diabetes. MEG will be given before the onset of diabetes in NOD mice and 24-48 hours after the onset of diabetes. Measurements will include NO synthase activity, pancreatic morphology, iNOS and nitrotyrosine immunohistochemistry. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE